Anticancer Efficacy and Toxicity of Oral GMO-paclitaxel in a Hormone Refractory Prostate Cancer Model.
10.4111/kju.2006.47.2.143
- Author:
Doo Bae KIM
1
;
Joon JANG
;
Yong Hyun CHO
;
Moon Soo YOON
;
He Sson CHUNG
;
Yeong Taek PARK
;
Young Wook CHOI
;
Sae Woong KIM
Author Information
1. Department of Urology, College of Medicine, The Catholic University of Korea. ksw1227@catholic.ac.kr
- Publication Type:Original Article
- Keywords:
Paclitaxel;
Hormone refractory prostate cancer
- MeSH:
Animals;
Cell Line;
Kidney;
Liver;
Mice;
Mice, Nude;
Paclitaxel;
Prostate*;
Prostatic Neoplasms*;
Tumor Burden
- From:Korean Journal of Urology
2006;47(2):143-149
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
PURPOSE: We wanted to evaluate the efficacy and toxicity of the newly developed oral glyceryl monooleate (GMO)-paclitaxel in a hormone refractory prostate cancer model. MATERIALS AND METHODS: A paclitaxel formulation was prepared from GMO, tricaprylin, Tween(R) 80 and paclitaxel. The tumor cells of prostate cancer (DU-145 cells) were incubated and then put into different paclitaxel concentrations. The tumoricidal activity was measured by using an indirect methylthiazol-2-yl-2,5-diphenyl tetrazolium bromide (MTT) assay. Cells of the DU-145 cell line were subcutaneously heterotransplanted into 18 nude mice, and they developed prostate cancer. The 18 mice were divided into 3 groups; the control group was injected with the DU-145 cell line (n=6), the GMO group was injected with GMO after the DU-145 cells were injected (n=6), and the oral GMO-paclitaxel group was injected with oral GMO-paclitaxel after the DU-145 cells were injected (n=6). The tumor volume was measured every week and the main organs were evaluated pathologically to determine the toxicity. RESULTS: On the MTT assay, the control group and the GMO group did not display cytotoxicity. However, treatment with the various GMO-paclitaxel formulations (0.1 microgram/ml, 1 microgram/ml, 10 microgram/ml) for treating the DU-145 cell line cancer induced cytotoxicity in a dose dependent fashion. The tumor volumes were not significantly changed in the group that was administered oral GMO-paclitaxel. However, there were significantly increased tumor volumes in the control group and the GMO group (p<0.05). Toxic changes were not detected in liver and kidney, and there was normal cellularity with a normal myeloid:erythroid ratio in the mice after the administration of oral GMO-paclitaxel. CONCLUSIONS: The newly developed oral GMO-paclitaxel has a remarkable cytotoxic effect against DU-145 cells without systemic toxicity. Therefore, oral GMO-paclitaxel therapy promises to be a safe and effective modality for treating hormone refractory prostate cancer, and it can possibly replace IV paclitaxel.
